A continuing aim of current science and technology is to mimic nature for assembly of different functional materials, with synthetic control at the molecular level. Natural systems are extremely efficient, and perform to their optimum under very mild conditions. Thus, a new scientific-technical field has developed around artificial “molecular mechanical systems”, as suggested by Osada et al. (1993) Progress In Polymer Science, 18:187-226. Such systems are structural-functional assemblies which convert energy from one form to another through changes in the structure or function. It is therefore desirable but somewhat problematic, to synthesize such materials with precise control at a molecular level such that changes in structure or structural interactions can cause an energy difference, resulting in a function or movement of the molecular mechanical system or assembly. Such molecular mechanical systems or assemblies have application in micro- and macro-intelligent systems, in controlled drug release, as artificial implants, as optical shutters, in molecular separation systems, and the like.
As pointed out by Osada (May 1993) Scientific American, pp.82-87, unlike natural materials, which are usually soft and wet, most industrial materials like metals, ceramics and plastics are dry and hard and so, cannot be used to make soft, bio-mimetic, and flexible materials. One class of materials, polymer gels, comes closer to natural systems in terms of soft-wet character. Polymer gels usually include an elastic, three dimensionally cross-linked network (provided by covalent bonds, physical entanglements, hydrogen bonding, Vander Waals forces, hydrophobic interactions), a fluid filling the interstitial space in the network. Their mechanical characteristics, optical properties, surface properties, sorption capacities, degree of swelling, etc., give them the ability to adapt to changes in their environment, thereby making them useful for various applications. Such materials that are capable of sensing a change in their environment and responding to them by altering one or more of their property coefficients are termed as “smart materials”. Gehrke, S. H. 1993) Advances in PolymerScience, 110:80-144 states that this “smart” ability can be finely tuned for a wide variety of applications, including switches, sensors, electromechanical-chemomechanical actuators, drug delivery devices, recyclable absorbents, specialized separation systems, bioreactors, bioassay systems, artificial muscles and display items, including light emitting diodes (LEDs), TV monitors, and the like.
The polymeric backbone of the polymer gel can be an organic or an inorganic network containing functional groups that are ionizable, amenable to red-ox reactions, photoactive, or capable of swelling by reversibly exchanging monovalent and divalent ions, as stated by Rossi et al. (1992) Journal of Intelligent Material System and Structure 3:75-95. The polymeric network can thus generate force by swelling or shrinking; or can undergo a reversible change in its volume in response to a change in its environment, temperature, solvent composition, mechanical strain, electric field, exposure to light, or the like, with no inherent limits in lifetime.
Extensive work has been done, and continues to be done with organic polymer gels having a hydrocarbon backbone which comprises a variety of functional groups, including -amine, -hydroxy, -amide, and -carboxyl. Gehrke, S. H. (1993) Advances in Polymer Science, 110:80-144 described the synthesis of organic polymer gels by techniques including co-polymerization/cross-linking of monomers, cross-linking of linear polymers by treatment with chemicals or gamma (y) radiation, and chemical conversion of one gel type to another.
Polymers made out of a single monomer have been used in a number of applications. For example, a neutral polymer gel of poly (vinyl alcohol) with water as a mobile component has been shown to undergo swelling, and to perform the mechanical work of lifting a load. Additionally, poly(silamine) telechelic oligomers, consisting of alternating 3,3-dimethyl-3-silapentane and N,N-diethylene units have been synthesized for use as high performance stimulus-sensitive materials, and as a poly(silamine) brush on glass and gold surfaces, as described by Nagasaki (March 1997) ChemTech, 23-29.
One of the most intensively studied responsive polymer gels has been cross-linked poly(N-isopropylacrylamide) (PNIPAAm). A number of environmental stimuli, including solvent, pH, temperature, electric fields, or electromagnetic radiation have been used to collapse or swell hydrogels made out of PNIPAAm, for use in various applications.
For example, PNIPAAm polymer gels were used by Feil et al. (July 1991) Journal of Membrane Science, 64:283-294 in molecular separation by thermosensitive membranes. PNIPAAm hydrogel membranes have been used to separate dextrans of molecular weights of 150,000 and 4,400 g/mol, respectively; and to separate uranine of molecular weight of 376 g/mol. The swelling characteristics can be influenced by an appropriate hydrophobic/hydrophilic balance in the hydrogel. Thus, this ratio has been used to vary the degree of swelling of these membranes. Such hydrogels also demonstrated a negative thermosensitivity, with the material showing dehydration at high temperature induced by hydrophobic interactions in the hydrogel. Thus, the hydrogel swelled under low temperature conditions and shrunk at higher temperatures. These swelling characteristics provided for permeability of the small molecules (uranine) at all temperatures (˜27° C.), followed by the 4,400 dextran at 23° C., and the 150,000 dextran at less than 20° C., thereby achieving separation of a mixture of molecules having a distinct difference in molecular size.
PNIPAAm hydrogels were characterized by Hoffinan et al. (1986) Journal of Controlled Release 4:213-222 as thermally reversible hydrogels. Particularly, PNIPAAm hydrogels have been observed to show, at a fixed pH, reversible shrinking and expansion at 50° C. and 4° C., respectively. The shrinking and expansion provides for the releasing and absorbing of biomolecules, including myoglobin and vitamin B12; and organic molecules, including Methylene Blue.
PNIPAAm hydrogels have also been applied as comb-type grafted hydrogels with rapid de-swelling response to temperature changes, as described by Yoshida et A (16 Mar. 1995) Nature 374:240-242. Hydrogels made of PNIPAAm with a comb structure undergo changes in volume in response to external stimuli like temperature. They collapse from their hydrated form to dehydrated form with increasing temperature because of hydrophobic interactions between the polymeric network.
PNIPAAm hydrogels have also been utilized in the synthesis and application of modulated polymer gels, as described by Hu et al. (July 1995) Science 260:525-527. Polymeric gels made of polyacrylamide interpenetrated by NIPAAm network have been made into bagel strip, a shape memory gel, and a gel “hand”. Each of these structures respond to environmental changes, such as change in temperature or change in acetone concentration.
To modify the properties of PNIPAAm polymers so as to tune their applicability, they have been co-polymerized with different monomers. For example, thermally responsive polymers for drug permeation and release have been described by Okano et al. (1990) Journal of Controlled Release 11:255-265. Polymers of PNIPAAm cross-linked with butyl-methacrylate and interpenetrating networks of polytetramethyleneetherglycol (PTMEG) show shrinking with increasing temperature. Particularly, the surface of the membrane shrinks, rather than the bulk, thereby regulating water and solute movement. The release of indomethacin (a model drug) has been studied with this system. At low temperatures, the release of the drug from the polymer followed pseudo zero order or first order kinetics, and at higher temperatures, it failed to diffuse out.
Dong et al. (1990) Journal of Controlled Release 13:21-31 state that thermally, reversible hydrogels made for PNIPAAm and bis-vinyl terminated polydimethylsiloxane (VTPDMS) show swelling-Shrinking behavior with respect to temperature and solvents. The gels swell in water and ethanol, permitting loading of hydrophilic and hydrophobic drugs at 25° C., and subsequent release in ethanol-water mixture at 37° C.
Polymeric systems of 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate and poly(vinyl alcohol) cross-linked with glutaraldehyde were used to prepare hydrogel beads for oral drug delivery as described by Kim et al. (August 1994) ChemTech pp. 36-39. Similar polymers have been used to make contact lenses, and have been used in implantation and transplantation surgery other than the controlled drug release systems, as described in Rossi et al. (1922) Journal of Intelligent Material System and Structure 3:75-95.
Despite the intensive study of organic polymer gels like cross-linked poly (N-isopropylacrylamide (PNIPAAm), there are many problems that limit application of such polymer gels as “smart” materials. For example, time consuming, multi-step synthesis processes which produce low yields and require harsh conditions unsuitable be utilized to synthesize the organic polymer gels. In addition, the synthesis of organic polymers require large amounts of precursors and other chemicals, which raises the overall cost of manufacture. The encapsulation of biological molecules in the organic polymers must be carried during post-synthesis steps, as the high temperatures that are required for preparation of these polymers are incompatible with biological molecules. Thus, the complexity of the overall process increases. Moreover, organic polymeric materials require presence of organic solvents for swelling/shrinkage, and therefore usage in biomedical drug delivery applications is, to a large extent, precluded. Therefore, there is a continuing need in the art for alternative materials to organic polymeric gels for application as “smart” materials.
One of the art-recognized methods of making inorganic polymeric gels with soft and characteristics is by the use of a sol-gel. Other art-recognized methods include solid-state reaction, melt-quenching, and vapor phase deposition methods. The sol-gel process utilizes mild synthesizing conditions, and thus offers flexibility in material design and synthesis at a molecular level. Particularly, Hench et al. (1990) Chemical Reviews 33-72 describe the sol-gel process as a process of making a three dimensional M-O-M polymeric network by hydrolysis and condensation process of appropriate alkoxy precursors. The reactions are generally described as follows:
Hydrolysis: Condensation:
Hydrolysis:-MOR + H20 -MOH + ROHCondensation:-MOH + ROM -MOM- + ROHOr-MOH + HOM -MOM- + H20
Thus, the factors which affect either or both of the above reactions are likely to have an impact on the properties of the gel. Faster hydrolysis and slower condensation results in small pore sized gel and slower hydrolysis and faster condensation result in bigger pore sized gel. If M is a silicon atom, then a Si—O—Si network, i.e., a glass-like material, is produced at room temperature.
Inorganic sol-gel materials have also been used to make chemical and biochemical sensors by encapsulating various kinds of organic and biomolecules as described, by Dave et al. (1994) Analytical Chemistry 66:1 120A-1127A. They have also been used to make electrochromic, photochromic, and thermochromic materials, i.e., change in color of the material with respect to changes in an electric field, temperature, respectively, etc., as described by Agerter (1999) Structure and Bonding 85:149-194. Despite the existence of various prior art “smart” materials having organic or inorganic polymer backbones, there remains much room for improvement in the art. Specifically, there exists a continuing need for improved “smart” materials that are relatively simple to synthesize and yet provide desirable levels of sensitivity to particular environmental stimuli.